Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University.
Drug Metab Pharmacokinet. 2013;28(5):435-8. doi: 10.2133/dmpk.dmpk-12-nt-136. Epub 2013 Feb 12.
It is known that rare but severe cutaneous adverse drug reactions (cADRs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS), are induced by carbamazepine (CBZ). Recent studies have shown an association between HLA-A31:01 and CBZ-induced severe cADRs in Japanese and Caucasian populations. In this study, we developed a simple method to detect the HLA-A31:01 allele by nested allele-specific primer-polymerase chain reaction combined with restriction fragment length polymorphism analysis. Accuracy of the developed method was evaluated by direct sequencing analysis of PCR products amplified from DNA samples with known HLA-A genotypes and by consigning diagnosis of DNA samples with unknown HLA-A genotypes to a company providing clinical laboratory testing. The method developed in this study is simple, rapid, and of low cost compared to outsourcing tests and may be useful for in-house testing of the HLA-A*31:01 allele.
已知卡马西平（CBZ）可引起罕见但严重的皮肤不良反应（cADRs），如史蒂文斯-约翰逊综合征（SJS）、中毒性表皮坏死松解症（TEN）和药物超敏反应综合征（DIHS）。最近的研究表明，HLA-A31:01 与日本和高加索人群中 CBZ 诱导的严重 cADRs 之间存在关联。在这项研究中，我们开发了一种通过巢式等位基因特异性引物聚合酶链反应结合限制性片段长度多态性分析来检测 HLA-A31:01 等位基因的简单方法。通过对具有已知 HLA-A 基因型的 DNA 样本进行 PCR 产物的直接测序分析，并将具有未知 HLA-A 基因型的 DNA 样本的诊断委托给提供临床实验室检测的公司，评估了所开发方法的准确性。与外包测试相比，本研究中开发的方法简单、快速且成本低，可用于 HLA-A*31:01 等位基因的内部测试。
